单中心73例儿童EB病毒脑炎临床特征

Clinical characteristics of 73 children with Epstein -Barr virus encephalitis

目的总结EB病毒脑炎（Epstein—Barr virus encephalitis，EBE）的临床特征，探讨影响不良预后的危险因素。方法回顾性分析2006年7月至2016年6月首都医科大学附属北京儿童医院收治的73例EBE的临床特点、实验室检查及影像学结果，进行电话随访评估预后。结果EBE全年散发，冬春季发病高于夏秋季，男女比例为1．5：1．0，年长儿多见，发病年龄中位数为5岁6个月。临床类型：脑膜脑炎型56例（75．7％），脱髓鞘型16例（21．9％），急性小脑共济失调1例（1．4％）。其中脑膜脑炎型包括脑膜脑炎24例（32．9％），脑炎22例（30．1％），脑膜炎10例（14．0％），脑炎并脊髓炎2例（2．7％），脑炎并视神经炎1例（1．4％）。仅2例存在传染性单核细胞增多症的典型症状，1例诊断慢性活动性EB病毒（EBV）感染，1例合并噬血细胞综合征。临床以发热（95．9％，70／73例）、惊厥（50．7％，37／73例）、意识改变（46．6％，34／73例）、呕吐（32．9％，24／73例）、头痛（28．8％，21／73例）为主要表现，可伴肝大（16．4％，12／73例），皮疹（13．7％，10／73例）及其他症状（15．0％，11／73例）。中枢神经系统阳性体征中，颈抵抗阳性42例（57．5％），巴氏征阳性32例（43．8％），肌力下降10例（13．7％），肌张力减低11例（15．1％），肌张力增高5例（6．8％），柯氏征阳性5例（6．8％），布氏征阳性2例（2．7％），22例（30．1％）缺乏中枢神经系统阳性体征。头颅磁共振成像异常者48例（45．8％），常见受累形式：细胞毒性水肿9例（12．7％），脱髓鞘改变8例（11．3％），脑萎缩样表现4例（5．6％）。受累部位：额叶14例（19．7％）、顶叶11例（15．5％）、颞叶11例（15．5％）、丘脑8例（11．3％）、基底核7例（9．9％）、枕叶6例（8．5％）、胼胝体5例（7．0％）等。随访到52例，失访21例，预后良好组44例（84．6％），预后不良组8例（15．4％），其中死亡3例（5．8％）。血清学检查符合EBV原发感染[即EBV-衣壳抗原（CA）-IgM＋，核抗原（NA）-IgG-]20例（29．9％），EBV既往感染再激活（即EBV—CA—IgM＋，NA—IgG＋）47例（70．1％），EBV原发感染或既往感染再激活状态在不同EBE临床类型与预后方面比较差异无统计学意义（P〉0．05）。对不同预后患儿各主要临床特征、EBV感染状态、基础疾病、合并其他病原体感染等方面进行比较发现，惊厥多发生在预后不良组（P=0．001）。结论EBE临床类型多样，可表现为脑膜脑炎、脑炎、脑膜炎、脱髓鞘及小脑共济失调等，脑实质可广泛受累，多数预后良好，存在惊厥者预后较差。

Objective To summarize the clinical features of Epstein -Barr virus encephalitis （EBE）, and to discuss the factors that could result in poor prognosis. Methods Seventy - three cases of EBE admitted to Beijing children＇s Hospital, Capital Medical University from July 2006 to June 2016 were collected. The clinical features,laboratory tests and imaging results were analyzed, and the follow- up check -up by phone was conducted. Results EBE could occur at any time of the year, and more cases occurred in winter/spring than in summer/autumn. Ratio of male to female patients was 1.5 ： 1. 0, and more eases occurred among the older children with their average age of 5 years and 6 months old. Specific types were ： meningoencephalitis 56 cases （ 75.7% ）, demyeliuation 16 cases （ 21.9% ）, and acute cerebellar ataxia 1 case（ 1.4% ）. EBE included 24 cases （32.9%） of meningoeneephalitis,22 cases （30.1%） of encephalitis, 10 cases （ 14.0% ） of meninges,2 cases （2.7%） combined with myelitis, and 1 case （ 1.4% ） combined with ophthalmoneuromyelitis. Only 2 cases were found with typical symptoms of infectious mononucleosis, 1 case was diagnosed as chronic Epsteinbait virus（EBV） infection,and 1 case was diagnosed as hemophagocytic histiocytosis. Clinical symptoms were ：70 eases （95.9%） of fever,37 eases （50.7%） of convulsion ,34 eases （46.6%） of altered state of consciousness,24 cases （32.9%） of vomit,and 21 cases （28.8%） of headache,which were found to be the primary symptoms, together with other symptoms,including 12 cases （ 16.4% ） of hepatomegaly, 10 cases （ 13.7% ） of rash, and 11 cases （ 15.0% ） of other symptoms. There were 42 cases （57.5 % ） of central nervous system（CNS） infection positive and neck stiffness,32 cases （43.8%） of Babinski＇s sign positive, 10 cases （13.7%） of decreased muscle strength,ll cases （15.1%） of atonia,5 cases （6.8%） of hypermyotonia,5 cases （6.8%） of coats disease positive, and 2 cases （2.7%） with Brudzinski signs. Twenty -two patients （30. 1% ） did not have CNS positive symptoms. There were 48 cases （45. 8% ） of magnetic resonance imaging （MRI） result showing abnormalities,with common symptoms including 9 cases （ 12.7% ） of cytotoxic edema,8 cases （ 11.3% ） of demyelination, and 4 cases （5.6%） with encephalanalosis symptoms. Affected organs included 14 cases （ 19.7% ） of frontal lobe, 11 cases （ 15.5% ） of parietal lobe,11 cases （ 15.5% ） of temporal lobe,8 cases （ 11.3% ） of thalamus,7 cases （9.9%） of basal ganglia,6 cases （8.5%） of occipital,and 5 cases （7.0%） of corpus callosum etc. Follow - up check - up was conducted on 52 cases, with 21 cases lost contact, and 44 cases （84. 6% ） with good prognosis, 8 cases （15.4%） with poor prognosis and 3 death cases （5.8%）. Serologic examinations found 20 cases （29.9%） of primary EBV infection [ EBV - capsid antigen（CA） -IgM ＋ and core antigen（NA） -IgG - ] ,47 cases （70.1%） of existed EBV infection being activated （ EBV - CA - IgM ＋ and NA - IgG ＋ ）, and there was no statistically significant difference in terms of clinical characteristics and prognosis. Convulsion occurs more frequently in group of poor prognosis （P = 0. 03 ） after comparing the aspects of main clinical features, stage of EBV infection, underlying diseases and combined with other infections etc （ P 〉 0.001 ）. Conclusions EBE can occur at various stage of EB infection. EBE can occur in various forms at clinic. CNS symptoms of meningoencephalitis, encephalitis, meninges , demyelination, and cerebellar ataxia etc. Patients＇ brain parenchyma can be affected extensively, and most of the patients experienced good prognosis, the virus can cause lethal infection;while patients with symptoms of convulsion may experience poor prognosis.